1. Field of the Invention
Embodiments of the invention relate to treatment of cancer with a monoclonal antibody to an S-phase regulated specific protein, particularly thymidine kinase.
2. Description of the Related Art
The S-phase is the portion of the cell cycle during which DNA replication takes place. Expression of genes related to DNA replication is maximal during early S-phase.
TK-1 is a cellular enzyme which is involved in a “salvage pathway” of DNA synthesis. In normal growing cells thymidine kinase 1 mRNA rises near the G1-S boundary, peaks in early S phase, and returns in G2 to approximately the level of early G1. It is activated in the G1/S phase of the cell cycle, and its activity has been shown to correlate with the proliferative activity of tumor cells. Malignant cells appear to have lost the strict regulation of TK1 that is observed in normal cells. TK activity is a major biochemical marker of cell proliferation and several studies show that TK levels are elevated in malignancies. The elevated TK activity is due to an increase in the TK1 isozyme. The elevation of TK1 levels in malignancies is not simply the result of cellular proliferation but is directly caused by alteration of regulatory mechanisms in cancer cells, which constitutively express TK1 mRNA.
The use of MAb to specifically target malignant cells is an approach which can leave normal or uninfected tissue or cells unharmed. MAbs may be used to construct therapeutic reagents with selectivity for certain populations of cells. Optionally, MAbs or other cell targeting proteins are linked to bioactive moieties to form biotherapeutic agents referred to as immunoconjugates, immunotoxins or fusion proteins, which can combine the selectivity of the targeting moiety with the potency of the bioactive moiety. Embodiments of the invention are directed to the use of anti-TK1 antibody to inhibit cell proliferation in cells that synthesize and overexpress TK1 such as cancer cells.
U.S. Pat. No. 5,698,409, which is incorporated herein by reference, describes a purified mammalian thymidine kinase 1 (TK1) from Raji cells and a TK1 monoclonal antibody. The monoclonal antibody binds to TK1 and inhibits TK1 activity. The TK1 monoclonal antibody was used for cancer diagnosis.